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The pharmacokinetics of cytarabine administered at three distinct subcutaneous dosing protocols in dogs with meningoencephalomyelitis of unknown origin
Author(s) -
Jones Aslynn,
McGrath Stephanie,
Gustafson Daniel L.
Publication year - 2019
Publication title -
journal of veterinary pharmacology and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.527
H-Index - 60
eISSN - 1365-2885
pISSN - 0140-7783
DOI - 10.1111/jvp.12809
Subject(s) - dosing , pharmacokinetics , medicine , pharmacology , area under the curve , adverse effect
The objective of this study was to evaluate the pharmacokinetics of the standard cytarabine (Ara‐C) protocol (50 mg/m 2 subcutaneously every 12 hr for 2 days) used for dogs with neuroinflammatory disease and compare it to two more practical protocols (a single 200 mg/m 2 subcutaneous dose and two 100 mg/m 2 subcutaneous doses every 12 hr). Four client‐owned dogs previously diagnosed with meningoencephalomyelitis of unknown origin were administered three distinct Ara‐C protocols with a 21‐day washout between each protocol. A complete blood count was performed seven days after each dosing protocol to assess for clinically relevant myelosuppression. No adverse events were observed. Plasma Ara‐C concentrations were measured using a validated liquid chromatography coupled to tandem mass spectrometry assay. The mean maximal concentrations in this study were 4,230, 9,293, and 16,675 ng/ml for a single dose of 50, 100, and 200 mg/m 2 , respectively. There was a linear relationship between dose and drug exposure. Drug exposure was similar regardless of the dosing protocol when the total dose was analyzed, with an area under the concentration versus time curve of 37,026, 38,465, and 32,510 ng × hr/ml for 50, 100, and 200 mg/m 2 , respectively.